Picking the point of inhibition: a comparative review of PI3K/AKT/mTOR pathway inhibitors

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• The phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is frequently activated in cancer.
• This pathway is critical for cancer cell growth and survival, making it a prime target for drug development.

Purpose of the Study:

• To review the literature on PI3K pathway inhibitors currently in clinical investigation.
• To differentiate the genomic contexts in which various PI3K inhibitors may demonstrate superior efficacy.

Main Methods:

• Literature review of clinical trials and preclinical studies.
• Analysis of different classes of PI3K pathway inhibitors, including dual PI3K/mTOR, pan-PI3K, isoform-specific PI3K, AKT, and mTOR inhibitors.
• Examination of the genomic landscape associated with inhibitor activity.

Main Results:

• An increasing number of PI3K pathway inhibitors are in clinical trials, targeting different components and isoforms.
• Inhibitors include ATP-competitive dual PI3K/mTOR, pan-PI3K, isoform-specific PI3K, AKT, and mTOR inhibitors.
• Understanding the genomic context is crucial for predicting patient response to specific inhibitors.

Conclusions:

• The diverse range of PI3K pathway inhibitors necessitates careful consideration of their mechanisms of action and the specific cancer's genomic profile.
• Identifying the optimal genomic context for each inhibitor class will enhance clinical trial design and therapeutic strategies.